The hygiene hypothesis: do we still believe in it?

Abstract

Numerous epidemiological studies suggest that there is an inverse relationship between allergic diseases and infections in early childhood, but there are also several well-conducted epidemiological studies that seemingly contradict this relationship. The maturation of the immature immune regulation after birth is largely driven by exposure to microbes. Germ-free animals manifest excessive immune responses when immunized and they do not develop normal immune regulation. The controversy regarding the role of infections for subsequently developing allergy is partly due to varying clinical definitions of 'allergy'. Thus, wheezing and asthma have often been included as outcomes. The hypothesis that commensal microbes are the normal stimulants for the maturation towards a balanced immune response is relevant for IgE-mediated disease manifestations, rather than recurrent bronchial obstruction per se. Epidemiological, clinical and animal studies taken together suggest that broad exposure to a wealth of commensal, non-pathogenic microorganisms early in life are associated with protection, not only against IgE-mediated allergies, but also conceivably against type-1 diabetes and inflammatory bowel disease. This has little relationship with 'hygiene' in the usual meaning of the word. The term 'hygiene hypothesis' is unfortunate, as it is misleading. A better term would be 'microbial deprivation hypothesis'.